Teerlink T, Neele S J M, de Jong S, Netelenbos J C, Stehouwer C D A
Department of Clinical Chemistry, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
Clin Sci (Lond). 2003 Jul;105(1):67-71. doi: 10.1042/CS20020309.
Oestrogen replacement therapy (ERT) has been shown to lead to favourable changes in the cardiovascular risk profile of postmenopausal women. Part of this effect is ascribed to increased production or bioavailability of nitric oxide (NO). We have tested the hypothesis that ERT lowers plasma levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of NO synthase (NOS). In a randomized double-blind study design, 40 hysterectomized postmenopausal women received conjugated equine oestrogen (CEE; 0.625 mg/day; n =14), the selective oestrogen receptor modulator raloxifene (150 mg/day; n =13) or placebo ( n =13). At baseline and after 6, 12 and 24 months of treatment, plasma was analysed for levels of arginine, ADMA, and symmetrical dimethylarginine (SDMA), a stereoisomer of ADMA that does not inhibit NOS. An overall treatment effect on ADMA levels was observed in the CEE group ( P =0.004 compared with placebo), but not in the raloxifene group ( P =0.50). The decrease of ADMA levels by CEE treatment was consistent over the 2-year study period, without significant differences between the effects at 6, 12 and 24 months. The average post-baseline change in ADMA in the CEE group compared with placebo was -7.8% (95% confidence interval -12.8% to -2.9%; P =0.003). Arginine or SDMA levels did not change during treatment in any of the groups. Thus ERT with oral conjugated oestrogen, but not with raloxifene, significantly reduced plasma concentrations of the cardiovascular risk factor ADMA in healthy postmenopausal women.
雌激素替代疗法（ERT）已被证明可使绝经后女性的心血管风险状况发生有益变化。这种作用部分归因于一氧化氮（NO）生成增加或生物利用度提高。我们检验了ERT可降低不对称二甲基精氨酸（ADMA，一种一氧化氮合酶（NOS）的内源性抑制剂）血浆水平的假说。在一项随机双盲研究设计中，40名子宫切除术后的绝经后女性接受了结合马雌激素（CEE；0.625毫克/天；n = 14）、选择性雌激素受体调节剂雷洛昔芬（150毫克/天；n = 13）或安慰剂（n = 13）治疗。在基线以及治疗6、12和24个月后，分析血浆中的精氨酸、ADMA以及对称二甲基精氨酸（SDMA，ADMA的一种不抑制NOS的立体异构体）水平。在CEE组观察到了对ADMA水平的总体治疗效果（与安慰剂相比，P = 0.004），但在雷洛昔芬组未观察到（P = 0.50）。CEE治疗导致的ADMA水平下降在为期2年的研究期间保持一致，6、12和24个月时的效果之间无显著差异。与安慰剂相比，CEE组ADMA的基线后平均变化为-7.8%（95%置信区间为-12.8%至-2.9%；P = 0.003）。在任何一组治疗期间，精氨酸或SDMA水平均未发生变化。因此，对于健康的绝经后女性，口服结合马雌激素进行ERT可显著降低心血管危险因素ADMA的血浆浓度，而雷洛昔芬则无此作用。
